A clinical study to investigate the safety of DEN-181 in rheumatoid arthritis patients

INTERVENTION: Randomised double blind, placebo‐controlled, single centre, single‐dose escalation study of DEN‐181 at three dose levels (4 active, 2 placebo per dose level). DEN‐181 is a liposomal formulation encapsulating two active pharmaceutical ingredients, calcitriol (0.6 ug/mL) and collagen II peptide (42 ug/mL; 15 amino acid peptide corresponding to collagen II protein 259‐273 (Proline 273 Hydroxyproline substitution). DEN‐181 is given by subcutaneous injection at a volume of 100 uL, 300 uL or 1000 uL. CONDITION: Rheumatoid Arthritis PRIMARY OUTCOME: Clinical safety observations including changes in: ; Vital signs, ; Symptom directed physical examination, ; Adverse events (graded according to Common Terminology Criteria for Adverse Events (CTCAE, Version 4.03)), ; Laboratory abnormalities (Haematology including ESR and Clinical chemistry including CRP in serum samples), ; Urinalysis ; SECONDARY OUTCOME: Determination of the concentration of calcitriol in plasma samples. Mean changes in DAS28CRPv4 (Disease Activity Score 28 including CRP assessment 4 variable calculation) scoring system. Phenotype of naïve, effector and regulatory T‐cells by flow cytometry Proportion and total number of naïve, effector and regulatory T‐cells by flow cytometry (composite outcome) ; ; INCLUSION CRITERIA: The criteria for entry into the study are: 1. Diagnosis of rheumatoid arthritis made by a rheumatologist; 2. HLA‐DRB1*0401+, HLA‐DRB1*0101+ or HLA‐DRB1*0401+HLA‐DRB1*0101+ heterozygotes, homozygotes or compound heterozygotes; and ACPA+ (anti‐CCP2>6); 3. Treatment with MTX at the same dose for at least 4 weeks prior to planned start of trial treatment; 4. Age 18‐75 years (male or female) inclusive; 5. Patients must be informed of the investigational nature of this study and give voluntary written informed consent in accordance with the institutional and hospital guidelines; 6. With or without swollen joints; 7. Male or Female. Females of child‐bearing potential must agree to use two effective forms of contraception from enrolment to completion of the study; 8. Blood glucose, CBC, haemoglobin, platelets, creatinine, bilirubin, and AST/ALT not greater than 1.5 times out of normal range at entry and clinically insignificant in